Early versus late surfactant replacement therapy in severe respiratory distress syndrome

26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III–IV), requirement of artificial ventilation and an FiO₂ ≥0.6. Nineteen neonates have been subjected to early treatment (2–15 h of age, mean birth weight SD: 1201 ± 387 g) and 7 patients to late treatment (> 15 h to 48 h of age, birth weight SD 1624 ± 649 g). Average FiO₂ before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO₂/FiO₂ ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to >21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD>21%O₂, >90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.     

Administration of recombinant human interleukin-7 to mice induces the exportation of myeloid progenitor cells from the bone marrow to peripheral sites

The administration of recombinant human interleukin-7 (rhIL-7) to mice twice a day for 7 days does not appreciably change bone marrow (BM) cellularity, but does result in a threefold to fivefold increase in the total number of leukocytes in the spleen, an eightfold to 10-fold increase in the total number of nonparenchymal cells (NPC) obtained from the liver, and up to a 20-fold increase in the total number of peripheral white blood cells (WBC). This regimen of rhIL-7 administration also causes a profound reduction in the total number of progenitors in the BM for both single-lineage colony-forming units- culture (CFU-c) (> 90%) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) (> 99%) colonies. In contrast, mice treated with rhIL-7 exhibited increases in both CFU-c (20- to 40-fold, 20-fold, and 15- to 40-fold) and CFU-GEMM (8- to 10-fold, 30-fold, and 6- to 10-fold) cultured from the peripheral blood, spleen, and NPC, respectively. The increase in CFU in the NPC was accompanied by a fivefold increase in the number of MAC-1+ cells and a ninefold increase in the number of 8C5bright+ cells. Splenectomy of mice before the administration of rhIL-7 further increased the total number of WBC, NPC, and myeloid progenitors as compared with the rhIL-7-treated nonsplenectomized mice. Finally, selective depletion of the BM by intraperitoneal administration of 89Sr (98% reduction in BM cellularity and > 99% reduction in BM myeloid progenitors) abrogated the rhIL-7- induced increases in cellularity and myeloid progenitor number in the peripheral blood, spleen, and NPC. These results show that the changes in myelopoiesis observed after in vivo administration of rhIL-7 to mice result largely from the emigration of myeloid progenitors from the BM through the blood to the spleen, liver, and, possibly, other peripheral organs.     

Auditory steady-state response, upper facial EMG, EEG and heart rate as predictors of movement during isoflurane-nitrous oxide anaesthesia

We have studied the relationship between patient movement andchanges in the auditory steady-state evoked potential, upperfacial muscle electromyogram (FEMG), electroencephalographic-zerocrossing frequency (EEG–ZCF) and heart rate during emergencefrom anaesthesia. Twelve healthy patients underwent surgeryduring stable isoflurane-nitrous oxide-oxygen anaesthesia withoutneuromuscular block. After skin closure, anaesthesia was discontinuedabruptly while mechanical ventilation was continued until thepatient moved. The magnitude of change in each physiologicalsignal was evaluated in decibels (dB). Both the auditory steadystate evoked potential and FEMG showed significant increasesin amplitude during the last 5-min period before movement (6.1and 10.7 dB, respectively). EEG-ZCF increased rapidly afteranaesthesia was discontinued (2.5 dB) but there was no furtherincrease in activity before movement. Heart rate did not changebefore movement. The use of the decibel transformation offersa promising method of displaying and interpreting changes inphysiological variables during anaesthesia.     

Tissue Culture of Cells Already in DNA Synthesis from Patients with Infectious Mononucleosis

1. Peripheral blood cultures from patients with infectious mononucleosiscontained approximately 50 times more cells incorporating tritiated thymidineat time 0 than normal cultures.

2. Cultures from these patients showed active cell division within thefirst 24 hours. No cell division was seen during this time in cultures of normal cells.

3. Cells dividing within the first 24 hours were identified as cells whichhad incorporated thymidine at time 0 by observation of metaphases containingtritiated thymidine.

4. Cell division ceased after 18-24 hours in the absence of phytohemagglutinin.

5. The data suggest that a population composed of immature lymphocyticcells in the circulation of patients with infectious mononucleosis is in theprocess of cell division. Proliferative capacity of peripheral blood cells cannot be studied adequately by ordinary morphologic technic.

Submitted on March 16, 1964 Accepted on November 11, 1964     

Stimulation of Thrombocytopoiesis in Irradiated Mice

Platelet depletion in mice, by injection of heterologous anti-platelet serum(APS), resulted in apparent stimulation of megakaryocytopoiesis as evidencedby a subsequent over-compensation of the level of circulating platelets. Injection of APS immediately before or after exposure to sublethal radiation or aday after exposure appeared to modify the response to radiation. Radiation-induced thrombocytopenia was neither as severe nor as prolonged in animalsso treated as in irradiated controls. More chronic thrombocytopenia at thetime of irradiation, however, appeared to increase the radiosensitivity of themegakaryocytic system.

Submitted on June 18, 1969 Accepted on January 13, 1970     

Megakaryocytopoiesis in the Rat

Labeling of rat megakaryocytes was observed after a single intravenousinjection of tritiated thymidine, and the following conclusions were made.

1. Morphologic appearance of megakaryocytes corresponded to their stageof maturation.

2. Only the youngest recognizable megakaryocytes (stage I) appeared tohave a DNA synthetic period.

3. Megakaryocytes did not undergo permanent cellular division.

4. There was probably some degree of ineffective megakaryocytopoiesis.

5. The average total maturation time of rat megakaryocytes was estimatedto be 43-75 hours wih 8-14 hours in stage I, 11-19 hours in stage II, and24-42 hours in stage III.

6. There was continuous influx into the megakaryocyte compartment froma precursor compartment. The immediate precursor cell was morphologicallyunrecognizable, but it appeared to have a generation time of 16 hours, aDNA synthesis period of 10 hours and a post-synthetic maturation timeof 2 hours.

7. Reutilization of tritium probably accounted for maintenance of a highdegree of labeling of megakaryocytes for a period of 1.5-4 days.

Submitted on August 7, 1964 Accepted on November 22, 1964